Activation and modulation of eosinophils by chemokines

Increased numbers of eosinophils in the peripheral blood and inflammatory t issue are characteristic features of allergic diseases such as allergic ast hma, rhinoconjunctivitis and atopic dermatitis. Tissue damage and propagati on of inflammation is thought to be mediated by the interaction between Th- 2-like T cells, antigen-presenting cells and eosinophils. In this process, eosinophils are activated by several inflammatory mediators such as GM-CSF, IL-5, eotaxin, eotaxin-2, RANTES, MCP-4 and C5a, leading to invasion of eo sinophils. At site of inflammation eosinophils release toxic proteins such as eosinophilic cation protein (ECP), major basic protein (MBP), eosinophil -derived neurotoxin (EDN) and reactive oxygen species leading to tissue dam age of the host. Reactive oxygen species are generated by the NADPH oxidase that can be activated by a number of different soluble agents (eotaxin, eo taxin-2, RANTES, MCP-4, C3a, C5a). Until now, there exists no specific ther apy to hinder the eosinophil response in allergic and non-allergic diseases . However, in the last years a number of factors could be characterized to modulate eosinophil effector functions that would be able to inhibit or ant agonize mediator-induced eosinophil activation. In this review, which is de voted to the 65(th) birthday of Professor Dr. L. Jager, we will focus on th e functional properties and the modulation of human eosinophils in inflamma tion. We will then discuss whether modulation of eosinophil effector functi ons might be successful as a future therapeutic strategy of diseases that a re accompanied with activated eosinophils.